Neoadjuvant botensilimab/balstilimab is active in resectable colon cancer, despite MMR status
Although data from a phase II trial (NCT05608044) demonstrated that botensilimab plus balstilimab was active in patients with relapsed/refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC) without liver metastases, the FDA advised against filing for accelerated approval of the combination since the objective response rates (ORRs) may not translate to a survival benefit, according to an announcement from Agenus following an end-of-phase II meeting
During the meeting, the FDA and Agenus reached an agreement on the recommended dose for a phase III study of 75 mg of botensilimab once every 6 weeks for up to 4 doses plus 240 mg of balstilimab once every 2 weeks for up to 2 years. Notably, the FDA also recommended the inclusion of a botensilimab monotherapy arm in the phase III study at the discretion of Agenus.
Interim topline data from the phase II study showed that patients treated with the 75-mg dose of botensilimab plus balstilimab (n = 62) experienced an ORR of 19.4% (95% CI, 10.4%-31.4%). In this arm, the 6-month overall survival (OS) rate was 90%. In patients given the 150-mg dose of botensilimab plus balstilimab (n = 61), the ORR was 8.2% (95% CI, 2.7%-18.1%). Notably, botensilimab monotherapy given at 75 mg once every 6 weeks (n = 38) and at 150 mg once every 6 weeks (n = 40) elicited ORRs of 0% (95% CI, 0%-9.3%) and 7.5% (95% CI, 1.6%-20.4%), respectively. In the standard-of-care (SOC) arm (n = 33), the ORR was 0% (95% CI, 0%-10.6%).
“Based on the high level of enthusiasm from significant numbers of global clinical experts and the promising clinical activity we have seen in the phase 1 and II studies, our commitment to seek all possible pathways to make botensilimab/balstilimab available to patients is unwavering,” Steven O’Day, MD, chief medical officer of Agenus, stated in a news release. “This includes exploring opportunities to partner in the United States to accomplish a successful phase III trial.